[Studies on Clostridium difficile and antimicrobial associated diarrhea or colitis].

Clostridium difficile has been implicated as the major cause of antimicrobial associated colitis or diarrhea. C. difficile was found in stools from 21 of 120 healthy subjects. C. difficile was found in stools from 8 of 9 patients with antimicrobial associated pseudomembranous colitis and in stools from 16 of 96 patients with antimicrobial associated diarrhea. The cytopathic toxin to HeLa cell neutralized by antitoxin to C. difficile was found in stools from all patients with antimicrobial associated colitis or diarrhea. Of 21 strains isolated in the stools from healthy subjects, 19 strains were toxigenic. Some of them were highly toxigenic strains. Such highly toxigenic strains, however, did not give rise to any clinical symptoms probably because of the limited number of this organisms in the normal flora of human intestines; the number of C. difficile ranged between less than 10 and 10(2) level per gram of stool when the organism was found. Of the 24 isolates from antimicrobial associated colitis or diarrheal patients, 4 were highly toxigenic. The susceptibilities of 65 isolates to various antimicrobial agents were determined by the agar dilution technique. All of the 65 strains were inhibited by low concentration of rifampicin, metronidazole, vancomycin, ampicillin and amoxicillin. The isolates were highly resistant to gentamicin, cefoxitin, cefotaxime and cefmenoxime. Wide variations in susceptibility of C. difficile strains to erythromycin, clindamycin and lincomycin were found. The studies have shown that subinhibitory concentrations of clindamycin, cephalothin and amoxicillin cause an increase in cytotoxin levels of C. difficile during broth culture. The increase in supernatant toxin levels occurs concomitant with a decrease in sonicated cell extract toxin levels. The data suggest that a number of factor can cause a release of toxin from C. difficile into the surrounding medium or the intestine.